A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis.
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Altemose, N., Noor, N., Bitoun, E., Tumian, A., Imbeault, M., Chapman, J. R., Aricescu, A. R., & et al. (2017). A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis.. eLife, 6 https://doi.org/10.7554/elife.28383
PRDM9 binding localizes almost all meiotic recombination sites in humans and mice. However, most PRDM9-bound loci do not become recombination hotspots. To explore factors that affect binding and subsequent recombination outcomes, we mapped human PRDM9 binding sites in a transfected human cell line and measured PRDM9-induced histone modifications. These data reveal varied DNA-binding modalities of PRDM9. We also find that human PRDM9 frequently binds promoters, despite their low recombination rates, and it can activate expression of a small number of genes including CTCFL and VCX. Furthermore, we identify specific sequence motifs that predict consistent, localized meiotic recombination suppression around a subset of PRDM9 binding sites. These motifs strongly associate with KRAB-ZNF protein binding, TRIM28 recruitment, and specific histone modifications. Finally, we demonstrate that, in addition to binding DNA, PRDM9's zinc fingers also mediate its multimerization, and we show that a pair of highly diverged alleles preferentially form homo-multimers.
Humans, Histone-Lysine N-Methyltransferase, DNA, Chromosome Mapping, Meiosis, Binding Sites, Protein Binding, Protein Multimerization, HEK293 Cells, Homologous Recombination
External DOI: https://doi.org/10.7554/elife.28383
This record's URL: https://www.repository.cam.ac.uk/handle/1810/279550
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/